Dr. Mary Gamble's research focuses on nutritional biochemistry at both basic and applied levels. Her earlier work on retinoid metabolism included studies on proteins involved in retinoid transport and in the generation of transcriptionally active retinoic acid metabolites. Dr. Gamble's international research began with studies on vitamin A deficiency in the Republic of the Marshall Islands and in Brazil. Since joining the Department of Environmental Health Sciences, Dr. Gamble's work has focused on nutrient/environment interactions, including the impacts of nutrients involved in one-carbon metabolism on the metabolism and toxicity of arsenic in Bangladesh. In randomized, controlled clinical trials (RCTs), Dr. Gamble's research has demonstrated that folic acid (FA) supplementation increases the methylation of arsenic to arsenical metabolites that are more rapidly excreted in urine, thereby lowering blood arsenic concentrations. A new direction of Dr. Gamble's work involves studies of the human metabolome using cutting-edge tools including untargeted high-resolution metabolomic (HRM) platforms that interrogate more than 80% of all metabolic pathways. Folic acid is a synthetic form of folate used to fortify foods in more than 80 countries and is used in vitamin supplements. Using banked samples from one of Dr. Gamble's completed RCTs, HRM will be used to evaluate the influence of FA supplementation and/or unmetabolized folic acid on downstream metabolites and pathways and identify those that may be linked to health outcomes. Another project investigates the metabolomic effects of exposure to arsenic and manganese in a chronically exposed population in Bangladesh. Her overall goal is to provide a conduit to advance knowledge gained from basic laboratory research into clinical research that informs public policy.
Office Location: 722 West 168th Street, ARB Suite 1107E
- Professor of Environmental Health Sciences
Credentials & Experience
Education & Training
- BS, 1988 Long Island University
- MS, 1993 Columbia University
- PhD, 1999 Columbia University
Committees, Societies, Councils
Honors & Awards
American Society for Nutrition Mary Swartz Rose Young Investigator Award, 2008
Calderone Award for Junior Faculty Development, 2007-2008
- Environmental Health
- Food Policy and Obesity
- Global Health
The Folic Acid and Creatine Trial: Treatment Effects of Supplementation on Arsenic Methylation Indices and Metabolite Concentrations in Blood in a Bangladeshi Population. Abuawad AK, Bozack AK, Navas-Acien A, Goldsmith J, Liu X, Hall MN, Ilievski V, Lomax-Luu AM, Parvez F, Shahriar H, Uddin MN, Islam T, Graziano JH, Gamble MV. Environ Health Perspect. 2023 Mar;131(3):37015. doi: 10.1289/EHP11270. Epub 2023 Mar 28. PMID: 36976258 Free PMC article. Clinical Trial.
Metabolomic changes associated with chronic arsenic exposure in a Bangladeshi population. Wu H, Kalia V, Niedzwiecki MM, Kioumourtzoglou MA, Pierce B, Ilievski V, Goldsmith J, Jones DP, Navas-Acien A, Walker DI, Gamble MV. Chemosphere. 2023 Apr;320:137998. doi: 10.1016/j.chemosphere.2023.137998. Epub 2023 Feb 4. PMID: 36746250
Nutrition, one-carbon metabolism and arsenic methylation. Abuawad A, Bozack AK, Saxena R, Gamble MV. Toxicology. 2021 Jun 15;457:152803. doi: 10.1016/j.tox.2021.152803. Epub 2021 Apr 24. PMID: 33905762 Free PMC article. Review.
Betaine and choline status modify the effects of folic acid and creatine supplementation on arsenic methylation in a randomized controlled trial of Bangladeshi adults. Bozack AK, Howe CG, Hall MN, Liu X, Slavkovich V, Ilievski V, Lomax-Luu AM, Parvez F, Siddique AB, Shahriar H, Uddin MN, Islam T, Graziano JH, Gamble MV. Eur J Nutr. 2021 Jun;60(4):1921-1934. doi: 10.1007/s00394-020-02377-z. Epub 2020 Sep 11.
PMID: 32918135 Free PMC article. Clinical Trial. Folic acid supplementation enhances arsenic methylation: results from a folic acid and creatine supplementation randomized controlled trial in Bangladesh. Bozack AK, Hall MN, Liu X, Ilievski V, Lomax-Luu AM, Parvez F, Siddique AB, Shahriar H, Uddin MN, Islam T, Graziano JH, Gamble MV. Am J Clin Nutr. 2019 Feb 1;109(2):380-391. doi: 10.1093/ajcn/nqy148. PMID: 30590411 Free PMC article. Clinical Trial.
Global Health Activities
Nutritional Influences on Arsenic Toxicity, Bangladesh: The largest known mass exposure to arsenic is presently occurring due to ground water contamination of well water throughout the Ganges-Brahmaputra Delta. There is a significant inter-individual variability in susceptibility to progression from arsenic exposure to clinical manifestations of arsenic toxicity (e.g. skin, lung, liver and bladder cancers). Several observational as well as biochemical studies have led to a prevalent hypothesis that nutritional status may account for a substantial portion of this variability, though no controlled clinical studies have addressed this important hypothesis. Methylation of inorganic arsenic (InAs) has generally been considered to be a detoxification pathway. InAs and DNA are both methylated via one-carbon metabolism, a biochemical pathway which is dependent on folate for de novo generation of one-carbon groups, and also uses vitamins B12 and B6 as cofactors. The primary hypothesis of this proposal is that nutritional regulation of one-carbon metabolism, specifically folate availability, contributes substantially to the large inter-individual variability observed in InAs and DNA methylation, and thus progression from arsenic exposure to toxicity. These hypotheses have been tested in a randomized, controlled folic acid supplementation trial of adults chronically exposed to arsenic-contaminated drinking water in Bangladesh. These studies have also revealed complex interations between arsenic exposure, folate deficiency and DNA methylation that influence risk for development of arsenic-induced premalignant skin lesions.
Folic acid and creatine as therapeutic approaches for lowering blood arsenic, Bangladesh: Arsenic (As) exposure affects more than 140 million people worldwide. Methylation of inorganic-arsenic (InAs) to methylarsonic- (MMA) and dimethylarsinic acids (DMA) relies on folate-dependent one-carbon metabolism and facilitates urinary arsenic (As) elimination. Our studies indicated that folate deficiency and hyperhomocysteinemia (HHcys) are associated with a reduced capacity to methylate As and are risk factors for As-induced skin lesions. Furthermore, folic acid (FA) supplementation significantly lowers blood As concentrations in individuals who are folate deficient. However, several fundamental questions still needed to be addressed: a) Does FA supplementation lower blood As concentrations in the general population? b) What is the optimal dose?, c) What is the time-course of the decline in blood As? d) Is there a rebound in blood As after the cessation of FA supplementation due to release of As from tissue stores? e) Can the ability of FA to lower blood As and homocysteine be enhanced by the addition of a novel new alternative approach: reduce methylation demand. The methylation of guanadinoacetate represents the final step in creatine biosynthesis. This reaction is the major consumer of methyl groups and every molecule of creatine synthesized ultimately generates a molecule of homocysteine. Furthermore, creatinine concentrations are a robust predictor of arsenic methylation. We tested the hypothesis that creatine supplementation, which downregulates endogenous creatine biosynthesis, will spare methyl groups, facilitate the methylation of other substrates - including As - and thereby lower blood As. To answer all of these questions, we conducted a randomized, double-blind, placebo controlled trial of FA (a comparison of two doses and durations), creatine, and creatine plus FA. Positive results of these interventions could have important therapeutic potential for ameliorating the long-term health consequences of As exposure for the many populations at risk.